Resolvins are a family of potent lipid mediators derived from both eicosapentaenoic acid and docosahexaenoic acid.[1] In addition to being anti-inflammatory, resolvins promote the resolution of the inflammatory response back to a non-inflamed state.[2] Resolvin D1 is produced physiologically from the sequential oxygenation of DHA by 15- and 5-lipoxygenase.[1] 17(R)-RvD1 is an aspirin-triggered epimer of RvD1 that reduces human polymorphonuclear leukocyte (PMN) transendothelial migration, the earliest event in acute inflammation, with equipotency to RvD1 (EC50 = ~30 nM).[3] 17(R)-RvD1 exhibits a dose-dependent reduction in leukocyte infiltration in a mouse model of peritonitis with maximal inhibition of ~35% at a 100 ng dose.[3] In contrast to RvD1, the aspirin-triggered form resists rapid inactivation by eicosanoid oxidoreductases. Analytical and biological comparisons of synthetic 17(R)-RvD1 with endogenously derived 17(R)-RvD1 have confirmed its identity as matching the natural product.[4]
Resolvin D1 is produced physiologically from the sequential oxygenation of docosahexaenoic acid by 15- and 5-lipoxygenase . It reduces human polymorphonuclear leukocyte transendothelial migration, the earliest event in acute inflammation, with an EC50 value of ~30 nM. RvD1 methyl ester is a methyl ester version of the free acid that may act as a lipophilic prodrug form that will alter its distribution and pharmacokinetic properties. The methyl ester moiety is susceptible to cleavage by intracellular esterases, leaving the free acid.
Prostaglandin D1 (PGD1) is the theoretical D-series metabolite of dihomo-γ-linolenic acid (DGLA), but to date it has not been isolated as a natural product. It is an inhibitor of ADP-induced platelet aggregation in humans with an IC50 value of 320 ng/ml, about 1/10 as potent as PGD2. 13,14-dihydro-15-keto Prostaglandin D1 (13,14-dihydro-15-keto PGD1) is the theoretical metabolite of PGD1 via the 15-hydroxy PG dehydrogenase metabolic pathway. No biological studies for this compound have been reported.
17(R)-Resolvin D1 (17(R)-RvD1) is an aspirin-triggered epimer of RvD1 that equivalently inhibits human polymorphonuclear leukocyte migration across the endothelium (EC50= ~30 nM), a precursor to acute inflammation. Unlike RvD1, it resists rapid degradation by eicosanoid oxidoreductases. In a mouse peritonitis model, 17(R)-RvD1 dose-dependently reduces leukocyte infiltration, achieving up to a 35% decrease with a 100 ng dose. Additionally, its methyl ester derivative, designed to enhance its pharmacokinetic and distribution properties as a more lipophilic prodrug, can be converted back into the active acid form by intracellular esterases.